Antibody therapies and diagnostics have been developed for use in treating a wide range of conditions including autoimmune diseases or disorders, infectious diseases, and cancers. Such therapies are useful but also can be associated with undesirable immunogenicity and can damage healthy cells and tissues.
B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) are two incurable B-cell malignancies with a combined incidence of new cases that exceeds 18,000 patients per year in the United States alone. Antibody therapies have been developed for B cell malignancies, which include rituximab, a chimeric mouse/human monoclonal antibody (mAb), alemtuzumab, a humanized mAb, and ofatumumab, a human mAb. However, the target antigens for all three of these drugs (CD20, CD52, and CD20 respectively) are expressed not only in malignant B cells but also in normal B cells, and CD52 is ubiquitously expressed on a variety of normal cells of the immune system. Therefore, immunosuppression can be a concern with these antibody therapies. Currently in the United States and Europe, there is no commercial therapeutic antibody that specifically recognizes an antigen present on malignant B cells, but not on normal B cells.
There is a desire for additional therapeutic and diagnostic antibodies having good efficacy and that exhibit minimal binding and/or damage to non-diseased cells.